Major Histocompatibility Complex - MHC Evolutionary Diversity

MHC Evolutionary Diversity

Most mammals have MHC variants similar to those of humans, who bear great allelic diversity, especially among the nine classical genes—seemingly due largely to gene duplication—though human MHC regions have many pseudogenes. The most diverse loci, namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600, and 870 known alleles, respectively. Many HLA alleles are ancient, sometimes of greater homology to a chimpanzee MHC alleles than to some other human alleles of the same gene.

MHC allelic diversity has challenged evolutionary biologists for explanation. Most posit balancing selection, which is any natural selection process whereby no single allele is absolutely most fit, such as frequency-dependent selection and heterozygote advantage. Recent models suggest that a high number of alleles is implausible via heterozygote advantage alone.

Pathogenic co-evolution, a counter-hypothesis, posits that common alleles are under greatest pathogenic pressure, driving positive selection of uncommon alleles—moving targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes, and remain circulating in a large population. Despite great MHC polymorphism at the population level, an individual bears at most 18 MHC I or II alleles.

Relatively low MHC diversity has been observed in the cheetah (Acinonyx jubatus), Eurasian beaver (Castor fiber), and giant panda (Ailuropoda melanoleuca). In 2007 low MHC diversity was attributed a role in disease susceptibility in the Tasmanian devil (Sarcophilus harrisii), native to the isolated island of Tasmania, such that an antigen of a transmissible tumor, involved in devil facial tumour disease, appears to be recognized as a self antigen. To offset inbreeding, efforts to sustain genetic diversity in populations of endangered species and of captive animals have been suggested.